Scientists Find Three New Gene Links to Alzheimer's

LONDON – Scientists have found three new major genetic links to Alzheimer's, affecting up to 20 percent of people with the brain-wasting disease, and said on Sunday it was the most significant such discovery in 15 years.

Two large studies found that the three new genes join the better-known APOE4 gene as significant risk factors for the most common cause of dementia.

"If we were able to remove the detrimental effects of these genes through treatments, we could reduce the proportion of people developing Alzheimer's by 20 percent," Julie Williams, a professor of Neuropsychological Genetics at Britain's Cardiff University, told a news conference in London.

Alzheimer's disease affects more than 26 million people globally, has no cure and no good treatment. The need for effective remedies is pressing, with the number of cases forecast to go beyond 100 million by 2050.

Current drugs can only delay the symptoms endured by patients, who lose their memories, the ability to find their way around and to care for themselves.

Williams, who led one of the two studies published in Nature Genetics, said that in Britain alone, eradicating the effects of the three new genes would mean almost 100,000 people could avoid the disease.

She said the findings were the most significant genetic discoveries for Alzheimer's in the 15 years since APOE4 was found to be linked, and said drug companies had shown a keen interest in their research.

MORE GENES OUT THERE TO CATCH

Williams and colleagues at Cardiff's Medical Research Council Center for Neuropsychiatric Genetics and Genomics carried out a genome-wide association study — a scan of the entire genetic map — involving more than 16,000 people from eight countries. They identified two new genes — called Clusterin and PICALM — that increase the risk of developing Alzheimer's.

A second genome-wide study conducted by Philippe Amouyel and colleagues at the Institut Pasteur de Lille in France, studied more than 6,000 people with Alzheimer's and nearly 9,000 healthy people in France, Belgium, Finland, Italy and Spain. They identified Clusterin and a third gene called CR1.

Amouyel said the disease risks associated with each gene were difficult to quantify, and said all three genes were relatively common. The scientists also stressed that an as yet unknown combination of many genetic and other environmental factors cause Alzheimer's.

The researchers said Clusterin may explain 10 percent of Alzheimer's cases, PICALM around 9 percent and CR1 4 percent. By comparison, 20 to 25 percent of Alzheimer's cases are linked to APOE.

Three gene variations have also been associated with rare, early-onset forms of Alzheimer's that run in families. Identifying the genes can help researchers understand the underlying causes of a disease and design drugs to fight them.

Michael Owen, director of the Cardiff center, said their study also found evidence that other genes could play a role in the risk of developing Alzheimer's.

"It's a bit like we have been fishing with a fishing net and we've pulled out some fish. We know there are more fish there, and with a finer mesh net we can catch them," he said.

The Cardiff team now plans a further study involving 60,000 participants to look deeper into genetic causes of Alzheimer's.